title: Evolutionary perspective on hepatitis B virus with an expanded sampling strategy.
abstract: To investigate the role hepatitis B e antigen (HBeAg) plays in the evolution of hepatitis B virus (HBV), we sequenced the basic core promoter (BCP) and precore (preC) regions of 348 clones total from ten HBV Chinese patients. Eleven mutations were more frequent in HBeAg-negative patients than in HBeAg-positive patients. Further, the sequencing of dozens of variants was found to be necessary to obtain mutation profiles. Phylogenetic and median-joining network analyses suggested that variants from each patient had a single common ancestor (monophyly). Higher haplotype and nucleotide diversities were identified in HBeAg-negative patients. Analysis of dN/dS suggested that viruses experiencing a stronger immune response had lower haplotype diversity. Because HBeAg seroconversion was associated with viral diversity it served as an indicator of HBV evolution. Significantly, this study indicated a larger sampling of variants from each patient was required to understand effectively the properties of HBV.
authors.affiliation: Institute of Clinical and Basic Medical Sciences, Center of Clinical Molecular Biology, Key Laboratory for Birth Defects and Genetic Diseases, First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
authors.forename: Jun-Dong
authors.initials: JD
authors.lastname: He
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Gao
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.forename: Robert W
authors.initials: RW
authors.lastname: Murphy
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D016000:Cluster Analysis; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006513:Hepatitis B e Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010802:Phylogeny; D017422:Sequence Analysis, DNA
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens
keywords: Evolution; HBeAg; Sampling strategy